The melanocortins include a family of peptide hormones that induce pigmentation by interaction with melanocortin-1 receptors (MC1R) in the epidermis.1 The primary pigmentary hormone that is released from the pars intermedia of the pituitary gland in some non-human animals, and from UV exposed keratinocytes in human skin, is alpha melanocyte stimulating hormone (alpha-MSH).1 This 13 amino acid peptide binds to MC1R to induce cyclic AMP-mediated signal transduction, which leads to the synthesis of melanin polymers from DOPA precursors.1 Two types of melanins can be expressed in humans. The brownish-black pigment eumelanin is believed to convey protection from sun damage, whereas the reddish, sulfur-containing pigment, pheomelanin, is often expressed in light-skinned human populations that report a poor tanning response to sunlight.2 These poorly-tanning, easily-burning populations often possess defects in the MC1R gene3 and are generally thought to be at a greater risk of developing both melanoma and non-melanoma skin cancers.4,5 
It has previously been disclosed that a super-potent derivative of alpha-MSH, Melanotan (Nle4-D-Phe7-alpha MSH, also referred to herein as “Melanotan-1” or “MT1”), can induce tanning in human volunteers.6 Melanotan contains two amino acid substitutions and is approximately 100 to 1,000-fold more potent than the native hormone at inducing pigmentation in experimental systems such as the frog skin bioassay or in cultured human keratinocytes.7 In humans, Melanotan primarily induces eumelanin synthesis in the skin in concert with its tanning effect.8 Although melanotropins have been postulated to affect immunologic changes, 9,10,11 all of the prior trials reported only minimal side effects such as facial flushing and transient GI upset, unless doses greater than those needed for tanning were administered.12 
There is compelling evidence that melanotropic peptides may provide a potential for increasing melanin pigmentation of human skin. Synthetic MSH may be used to enhance skin pigmentation of normal or light-skinned individuals to protect them from the hazards of solar radiation. Several studies have suggested that individuals whose skin tends to burn easily on exposure to the sun and does not tan readily are at higher risk of both nonmelanoma skin tumors and of cutaneous melanoma.16,17,18 There is unambiguous evidence that UV radiation is responsible for skin cancer in humans. In the face of increased deterioration of the ozone layer and the increasing incidence of and mortality from skin cancer, the ability to stimulate the skin's own “protective mechanism” of tanning may prove extremely important as photoprotective strategy.
Accordingly, described herein are methods for inducing melanogenesis in a human subject by administering alpha-MSH analogues to the subject at greatly reduced plasma levels, which surprisingly leads to increased melanin density levels in the subject. By increasing melanin levels in a subject, it is possible to reduce or prevent the occurrence of UV radiation-induced skin damage in the subject. Additionally, the reduced amount of alpha-MSH analogue that is required in the methods described herein avoids undesirable side effects associated with higher doses.